7. Project Summary/Abstract This proposal requests funding to support the conduct of the juvenile toxicology study of SGX942 (dusquetide); the first step of embarking on a larger SGX942 pediatric development program. The major objectives of the study are to confirm the safety of SGX942 in a juvenile population and to facilitate a safety study in a pediatric patient population at high risk of developing severe oral mucositis (SOM). Mucositis is the clinical term for the painful inflammation and ulceration of the mucous membranes lining the digestive tract, usually as an adverse effect of chemotherapy/radiotherapy treatment for cancer. The mechanisms of mucositis have been linked to exaggerated response of the innate immune system to the tumor therapy induced tissue damage. Bacterial infection of the ulcerative lesions is now regarded as a secondary consequence of dysregulated local inflammation triggered by therapy-induced cell death, rather than as the primary cause of the lesions. The pathophysiology of OM is similar in adults and children with the main driver of OM intensity and duration being the chemotherapy and/or radiation treatment protocol. In the pediatric population, OM is a frequent (40-70%) significant side effect of chemotherapy and radiation treatment used in a variety of underlying diseases including allogeneic hematopoietic stem cell transplantation, solid tumors, and hematologic cancers, and for most tumor types there is no efficacious therapy available to treat the primary pathology. OM in pediatrics is often more frequent and more severe than in adults and has substantial impact on the quality of life, serious infection rates, and impacts the decisions about the duration and intensity of the chemoradiation therapy that, in turn, can impact survival. Preclinical studies with SGX942 revealed a significant reduction in both duration and peak intensity of oral mucositis caused by either fractionated radiation or chemotherapy. In animal studies, SGX942 does not interfere with recovery from leukopenia and is equally effective in leukopenic animals, while also providing anti-infective activity. IDRs have been shown to not interfere with responses of the adaptive immune system (generation of antibodies, Clinically, SGX942 has demonstrated statistically significant reduction of at least 50% duration of SOM in adult head and neck cancer patients undergoing chemoradiation therapy and is being evaluated in Phase 3 study in this same population. The innate immune system is highly conserved and generally established by 2 years of age; therefore SGX942 is expected to be equally efficacious in both adults and children. Testing in adolescent/young adult animals has demonstrated both anti- inflammatory and anti-infective activity. There is no currently approved therapy for OM in non-hematological malignancies and the only approved therapy in hematological malignancies is not considered efficacious in the context of allogeneic stem cell transplantation. The specific aim of the proposal is to confirm the safety of SGX942 compared to placebo in juvenile animals with maturing immune systems, including evaluation of the adaptive immune system (NK, T and B cells).